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Organoids as self-organized structure derived from stem cells can recapitulate the function of an organ in miniature form which have developed great potential for clinical translation, drug screening and personalized medicine. Nevertheless, the majority of patient-derived organoids (PDOs) are currently being cultured in the basement membrane matrices (BMMs), which are constrained by xenogeneic origin, batch-to-batch variability, cost, and complexity. Besides, organoid culture relies on biochemical signals provided by various growth factors in the composition of medium. We propose sodium alginate hydrogel scaffold in addition to the fibroblast conditioned medium (FCM)-enriched culture medium that is inexpensive and easily amenable to clinical applications for the culture of bladder cancer PDOs. PDOs grown in sodium alginate and FCM based medium have proliferation potential, growth rate, and gene expression that are similar to PDOs cultured in BME. According to the results, sodium alginate has substantial mechanical properties and reduces variance in early passage bladder tumor organoid cultures collected from patients. Furthermore, using FCM based medium as an alternative solution to eliminate some essential growth factors can be considered, especially for low-resource situation and develop cost effective tumor organoids., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

An electrochemical sensory platform is presented for determination of sumatriptan (SUM) in aqueous solutions and human blood serum. A pencil graphite electrode (PGE) was electrochemically delaminated by cyclic voltammetry technique, and then further modified using nanoparticles of a zinc-based metal-organic framework (Zn(II)-MOF). The fabricated Zn(II)-MOF/EDPGE electrode was utilized for sensitive electrochemical detection of SUM via an electro-oxidation reaction. The Zn(II)-MOF was hydrothermally synthesized and characterized by various techniques. The electrochemical delamination of PGE results in a porous substrate, facilitating the effective immobilization of the modifier. The designed sensor benefits from both enhanced surface area and an accelerated electron transfer rate, as evidenced by the chronocoulogram and Nyquist plots. Under optimized conditions, the developed sensor exhibited a linear response for 0.99-9.52 µM SUM solutions. A short response time of 5 s was observed for the fabricated sensor and the detection limit was found to be 0.29 μM. Selectivity of Zn(II)-MOF/EDPGE towards SUM was evaluated by examining the interference effect of codeine, epinephrine, acetaminophen, ascorbic acid, and uric acid, which are commonly found in biological samples. The developed sensor shows excellent performance with recovery values falling within the range of 96.6 to 111% for the analysis of SUM in human blood serum samples., (© 2023. Springer Nature Limited.)

Fully automated and volumetric segmentation of critical tumors may play a crucial role in diagnosis and surgical planning. One of the most challenging tumor segmentation tasks is localization of pancreatic ductal adenocarcinoma (PDAC). Exclusive application of conventional methods does not appear promising. Deep learning approaches has achieved great success in the computer aided diagnosis, especially in biomedical image segmentation. This paper introduces a framework based on convolutional neural network (CNN) for segmentation of PDAC mass and surrounding vessels in CT images by incorporating powerful classic features, as well. First, a 3D-CNN architecture is used to localize the pancreas region from the whole CT volume using 3D Local Binary Pattern (LBP) map of the original image. Segmentation of PDAC mass is subsequently performed using 2D attention U-Net and Texture Attention U-Net (TAU-Net). TAU-Net is introduced by fusion of dense Scale-Invariant Feature Transform (SIFT) and LBP descriptors into the attention U-Net. An ensemble model is then used to cumulate the advantages of both networks using a 3D-CNN. In addition, to reduce the effects of imbalanced data, a multi-objective loss function is proposed as a weighted combination of three classic losses including Generalized Dice Loss (GDL), Weighted Pixel-Wise Cross Entropy loss (WPCE) and boundary loss. Due to insufficient sample size for vessel segmentation, we used the above-mentioned pre-trained networks and fine-tuned them. Experimental results show that the proposed method improves the Dice score for PDAC mass segmentation in portal-venous phase by 7.52% compared to state-of-the-art methods in term of DSC. Besides, three dimensional visualization of the tumor and surrounding vessels can facilitate the evaluation of PDAC treatment response., (© 2022. The Author(s).)

Given the capacity of Optical Coherence Tomography (OCT) imaging to display structural changes in a wide variety of eye diseases and neurological disorders, the need for OCT image segmentation and the corresponding data interpretation is latterly felt more than ever before. In this paper, we wish to address this need by designing a semi-automatic software program for applying reliable segmentation of 8 different macular layers as well as outlining retinal pathologies such as diabetic macular edema. The software accommodates a novel graph-based semi-automatic method, called "Livelayer" which is designed for straightforward segmentation of retinal layers and fluids. This method is chiefly based on Dijkstra's Shortest Path First (SPF) algorithm and the Live-wire function together with some preprocessing operations on the to-be-segmented images. The software is indeed suitable for obtaining detailed segmentation of layers, exact localization of clear or unclear fluid objects and the ground truth, demanding far less endeavor in comparison to a common manual segmentation method. It is also valuable as a tool for calculating the irregularity index in deformed OCT images. The amount of time (seconds) that Livelayer required for segmentation of Inner Limiting Membrane, Inner Plexiform Layer-Inner Nuclear Layer, Outer Plexiform Layer-Outer Nuclear Layer was much less than that for the manual segmentation, 5 s for the ILM (minimum) and 15.57 s for the OPL-ONL (maximum). The unsigned errors (pixels) between the semi-automatically labeled and gold standard data was on average 2.7, 1.9, 2.1 for ILM, IPL-INL, OPL-ONL, respectively. The Bland-Altman plots indicated perfect concordance between the Livelayer and the manual algorithm and that they could be used interchangeably. The repeatability error was around one pixel for the OPL-ONL and < 1 for the other two. The unsigned errors between the Livelayer and the manual algorithm was 1.33 for ILM and 1.53 for Nerve Fiber Layer-Ganglion Cell Layer in peripapillary B-Scans. The Dice scores for comparing the two algorithms and for obtaining the repeatability on segmentation of fluid objects were at acceptable levels.

Fuchs uveitis (FU) is a chronic and often unilateral ocular inflammation and characteristic iris atrophic changes, other than heterochromia, are common in FU and are key to the correct diagnosis in many cases. With the advent of anterior segment optical coherence tomography (AS-OCT), some investigators attempted to quantitatively study these atrophic changes; mostly by introducing various methods to measure iris thickness in AS-OCT images. We aimed to present an automated method in an observational case series to measure the smoothness index (SI) of the iris surface in AS-OCT images. The ratio of the length of the straight line connecting the most peripheral and central points of the anterior iris border (in nasal and temporal sides) to the actual length of this border on AS-OCT images, was defined as SI. In a uveitis referral center, twenty-two eyes of 11 patients with unilateral Fuchs uveitis (FU) (7 female) and 22 eyes of 11 healthy control subjects underwent AS-OCT imaging. Image J and a newly developed MATLAB algorithm were used for manual and automated SI measurements, respectively. Agreement between manual and automated measurements was evaluated with Bland-Altman analysis and interclass correlation coefficient. The inter-eye difference of SI was compared between the FU group and the control group. Automated mean overall SI was 0.868 ± 0.037 and 0.840 ± 0.039 in FU and healthy fellow eyes, respectively (estimated mean difference =  - 0.028, 95% CI [- 0.038, - 0.018], p < 0.001). Bland- Altman plots showed good agreement between two methods in both healthy and FU eyes. The interclass correlation coefficient between the manual and automated measurements in the FU and healthy fellow eyes was 0.958 and 0.964, respectively. The inter-eye difference of overall SI was 0.029 ± 0.015 and 0.012 ± 0.008 in FU group and control group, respectively (p = 0.01). We concluded that the automated algorithm can rapidly and conveniently measure SI with results comparable to the manual method.

There is a major challenge to attach nanostructures on to the electrode surface while retaining their engineered morphology, high surface area, physiochemical features for promising sensing applications. In this study, we have grown vertically-aligned ZnO nanorods (NRs) on fluorine doped tin oxide (FTO) electrodes and decorated with CuO to achieve high-performance non-enzymatic glucose sensor. This unique CuO-ZnO NRs hybrid provides large surface area and an easy substrate penetrable structure facilitating enhanced electrochemical features towards glucose oxidation. As a result, fabricated electrodes exhibit high sensitivity (2961.7 μA mM -1  cm -2 ), linear range up to 8.45 mM, low limit of detection (0.40 μM), and short response time (<2 s), along with excellent reproducibility, repeatability, stability, selectivity, and applicability for glucose detection in human serum samples. Circumventing, the outstanding performance originating from CuO modified ZnO NRs acts as an efficient electrocatalyst for glucose detection and as well, provides new prospects to biomolecules detecting device fabrication.

Wnt signalling maintains the undifferentiated state of intestinal crypt/progenitor cells through the TCF4/beta-catenin-activating transcriptional complex. In colorectal cancer, activating mutations in Wnt pathway components lead to inappropriate activation of the TCF4/beta-catenin transcriptional programme and tumourigenesis. The mechanisms by which TCF4/beta-catenin activate key target genes are not well understood. Using a proteomics approach, we identified Tnik, a member of the germinal centre kinase family as a Tcf4 interactor in the proliferative crypts of mouse small intestine. Tnik is recruited to promoters of Wnt target genes in mouse crypts and in Ls174T colorectal cancer cells in a beta-catenin-dependent manner. Depletion of TNIK and expression of TNIK kinase mutants abrogated TCF-LEF transcription, highlighting the essential function of the kinase activity in Wnt target gene activation. In vitro binding and kinase assays show that TNIK directly binds both TCF4 and beta-catenin and phosphorylates TCF4. siRNA depletion of TNIK followed by expression array analysis showed that TNIK is an essential, specific activator of Wnt transcriptional programme. This kinase may present an attractive candidate for drug targeting in colorectal cancer.

Enhancers have been defined as cis-acting DNA sequences that stimulate transcription from a linked promoter in a distance- and orientation-independent manner. How enhancers activate gene transcription over vast chromosomal distances within metazoan genomes remains poorly understood. Here, we show that the transcription factor GAGA can stimulate transcription by linking an enhancer to its cognate promoter. Strikingly, in addition to facilitating activation by a remote enhancer in cis, GAGA can direct activation of a promoter by an enhancer located on a separate DNA molecule. Enhancer function in trans is critically dependent on POZ domain-mediated GAGA oligomerization, enabling GAGA to bind two DNA molecules simultaneously. Transcriptional activation by an enhancer functioning in trans was observed both in transfected cells and in reconstituted transcription reactions. We propose that GAGA facilitates long-range activation by providing a protein bridge that mediates enhancer-promoter communication.

The Polycomb group (PcG) of repressors and the trithorax group (trxG) of activators maintain the correct expression of several key developmental regulators, including the homeotic genes. PcG and trxG proteins function in distinct multiprotein complexes that are believed to control transcription by changing the structure of chromatin, organizing it into either a 'closed' or an 'open' conformation. The hallmark of gene regulation by PcG/trxG proteins is that it can lead to a mitotically stable pattern of gene expression, often referred to as epigenetic regulation. Although much remains to be learned, recent studies have provided insights into how this epigenetic switch is set, how PcG/trxG proteins might be linked to cis-acting DNA elements and what potential mechanisms underlie stable inheritance of gene expression status over multiple cell divisions. Finally, the study of the evolutionarily conserved PcG/trxG factors has recently gained additional urgency with the realization that they play a pertinent role in certain human cancers.